Strongyloides stercoralis is a neglected parasite that can cause death in immunocompromised individuals. There were no data on the epidemiology of S. stercoralis infection in San Marino Republic until two patients (one of whom died) were diagnosed with severe strongyloidiasis (hyperinfection) between September 2016 and March 2017. A serology test for Strongyloides spp. was introduced in routine practice in the laboratory of the State Hospital to test patients considered to be at risk for strongyloidiasis. Between August 2017 and August 2018, of 42 patients tested with serology, two (4.8%) were positive. An additional case was found by gastric biopsy. Two of the positive cases were presumably autochthonous infections (elderly people with no significant travel history), while the other was a probable imported case (young man born in Nigeria and settled in Europe since 2003). Epidemiology of strongyloidiasis in San Marino might be similar to Northern Italy, where a relevant proportion of cases was diagnosed in immigrants (mainly from sub-Saharan Africa) and in elderly Italians with eosinophilia. Screening for strongyloidiasis might be worthwhile in inhabitants of San Marino in the same categories of individuals, particularly those at risk of immune suppression.